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V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.

Publication ,  Journal Article
van Eeden, C; Wibmer, CK; Scheepers, C; Richardson, SI; Nonyane, M; Lambson, B; Mkhize, NN; Vijayakumar, B; Sheng, Z; Stanfield-Oakley, S ...
Published in: Cell Rep
December 11, 2018

Antibodies that bind residue K169 in the V2 region of the HIV-1 envelope correlated with reduced risk of infection in the RV144 vaccine trial but were restricted to two ED-motif-encoding light chain genes. Here, we identify an HIV-infected donor with high-titer V2 peptide-binding antibodies and isolate two antibody lineages (CAP228-16H/19F and CAP228-3D) that mediate potent antibody-dependent cell-mediated cytotoxicity (ADCC). Both lineages use the IGHV5-51 heavy chain germline gene, similar to the RV144 antibody CH58, but one lineage (CAP228-16H/19F) uses a light chain without the ED motif. A cocrystal structure of CAP228-16H bound to a V2 peptide identified a IGLV3-21 gene-encoded DDxD motif that is used to bind K169, with a mechanism that allows CAP228-16H to recognize more globally relevant V2 immunotypes. Overall, these data further our understanding of the development of cross-reactive, V2-binding, antiviral antibodies and effectively expand the human light chain repertoire able to respond to RV144-like immunogens.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 11, 2018

Volume

25

Issue

11

Start / End Page

3123 / 3135.e6

Location

United States

Related Subject Headings

  • Tissue Donors
  • Protein Binding
  • Peptides
  • Models, Molecular
  • Lysine
  • Immunoglobulin Light Chains
  • Humans
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
 

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van Eeden, C., Wibmer, C. K., Scheepers, C., Richardson, S. I., Nonyane, M., Lambson, B., … Morris, L. (2018). V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity. Cell Rep, 25(11), 3123-3135.e6. https://doi.org/10.1016/j.celrep.2018.11.058
Eeden, Charmaine van, Constantinos Kurt Wibmer, Cathrine Scheepers, Simone I. Richardson, Molati Nonyane, Bronwen Lambson, Nonhlanhla N. Mkhize, et al. “V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.Cell Rep 25, no. 11 (December 11, 2018): 3123-3135.e6. https://doi.org/10.1016/j.celrep.2018.11.058.
van Eeden C, Wibmer CK, Scheepers C, Richardson SI, Nonyane M, Lambson B, et al. V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity. Cell Rep. 2018 Dec 11;25(11):3123-3135.e6.
van Eeden, Charmaine, et al. “V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity.Cell Rep, vol. 25, no. 11, Dec. 2018, pp. 3123-3135.e6. Pubmed, doi:10.1016/j.celrep.2018.11.058.
van Eeden C, Wibmer CK, Scheepers C, Richardson SI, Nonyane M, Lambson B, Mkhize NN, Vijayakumar B, Sheng Z, Stanfield-Oakley S, Bhiman JN, Bekker V, Hermanus T, Mabvakure B, Ismail A, Moody MA, Wiehe K, Garrett N, Karim SA, Dirr H, Fernandes MA, Sayed Y, Shapiro L, Ferrari G, Haynes BF, Moore PL, Morris L. V2-Directed Vaccine-like Antibodies from HIV-1 Infection Identify an Additional K169-Binding Light Chain Motif with Broad ADCC Activity. Cell Rep. 2018 Dec 11;25(11):3123-3135.e6.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

December 11, 2018

Volume

25

Issue

11

Start / End Page

3123 / 3135.e6

Location

United States

Related Subject Headings

  • Tissue Donors
  • Protein Binding
  • Peptides
  • Models, Molecular
  • Lysine
  • Immunoglobulin Light Chains
  • Humans
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies